This invention relates in general to a preparation having anti-inflammatory, and particularly anti-arthritic, activity which is a lipid extract of mussels, including the New Zealand green lipped mussel, Perna canaliculus, and the blue mussel Mytilus edulis. 
There is at the present time a significant medical need for new anti-inflammatory and anti-arthritic drugs with reduced side effects and prolonged in vivo activity and in particular for compounds which will moderate the progress of the arthropathies. Plants and other living cells offer a vast reservoir of compounds which have pharmacological effects on humans. Natural products have frequently been the source of effective drugs and lately there has been an increased interest in the analysis of these natural products, especially where a clinical benefit is claimed. Marine organisms contain metabolites that can act as pharmacological agents and aid in the treatment of inflammation.
An anti-inflammatory activity of Perna canaliculus (New Zealand Green Lipped Mussel) was first implicated as part of a pharmacological study on leukaemia. Initial assessment of the anti-inflammatory activity of Perna canaliculus was first attempted using a polyarthritis model in rats1. These studies however failed to show the presence of any significant anti-inflammatory activity in the mussel preparation. In contrast, Miller and Ormrod2 using a carrageenin-induced paw oedema assay3, were able to show that mussel preparations, when administered intraperitoneally, gave a significant reduction in the swelling of a carrageenin-induced rat paw oedema. Subsequently, they fractionated a non-dialysable, water-soluble fraction from the mussel preparation that possessed anti-inflammatory activity. The aqueous extract showed a dose-ependent anti-inflammatory activity when administered intraperitoneally and could not be detected upon oral administration of the mussel powder. It was suggested that the water-soluble fraction therefore contained an irritant component possessing apparent anti-inflammatory activity.
Rainsford and Whitehouse4 also reported that freeze-dried powdered preparations of the whole mussel given orally to rats showed some modest anti-inflammatory activity in the carrageenin-induced paw oedema assay, and that this material strikingly reduced the gastric ulcerogenicity of several non-steroidal anti-inflammatory drugs in rats and pigs.
Use of the whole mussel extract in the treatment of both rheumatoid arthritis and osteoarthritis in human patients has also been reported5.
Initial work leading to the present invention based on lipid extracts from Perna canaliculus powder prepared using solvent extraction techniques (in contrast to earlier work on aqueous fractions), established that the lipid fractions show a measure of anti-inflammatory activity when tested in appropriate model systems. A reliable source of lipid extract of Perna canaliculus and Mytilus edulis has subsequently become available through the procedure of supercritical fluid extraction (SFE). The lipid extract is obtained as a dark yellow-brown viscous oil exhibiting strong ultraviolet absorbing character which is consistent in physical data to lipid extracts obtained from earlier solvent extraction procedures.
Accordingly to one aspect, the present invention provides a method of anti-inflammatory treatment of a human or animal patient, which comprises administration to the patient of an effective amount of a lipid extract of Perna canaliculus or Mytilus edulis. 
In another aspect, the present invention provides an anti-inflammatory composition comprising a lipid extract of Perna canaliculus or Mytilus edulis as an active component thereof, together with one or more pharmaceutically acceptable carriers and/or diluents.
In yet another aspect, the invention extends to the use of a lipid extract of Perna canaliculus or Mytilus edulis in the preparation of a composition for anti-inflammatory treatment of a human or animal patient.
The terms xe2x80x9canti-inflammatory treatmentxe2x80x9d and xe2x80x9canti-inflammatory compositionxe2x80x9d as used herein, relate to treatment of, or compositions for treatment of inflammatory conditions in general, including arthritic conditions such as osteoarthritis and rheumatoid arthritis, as well as in treatment of multiple sclerosis and various viral infections. Activity of a compound for use in such treatment may be demonstrated using standard assays, for example using a carrageenin-induced paw oedema assay or by the ability to beneficially limit the onset or progression of an experimental polyarthritis, as described in detail herein.
Preferably, the lipid extract which is used in the treatment or composition of the present invention is an extract prepared by supercritical fluid extraction (SFE) of freeze-dried powdered mussel using a cryogenic fluid (such as cryogenic fluid CO2) as the extracting medium. In comparison to solvent extraction techniques, supercritical fluid extraction using cryogenic fluid CO2 produces a lipid extract rich in non-polar lipids, particularly in free fatty acids. While the exact composition of the lipid extract has not yet been established, it is known to contain not only free fatty acids (including unsaturated fatty acids), but also triglycerides and cholesterol esters.
A variety of administration routines are available. The particular mode selected will depend, of course, upon the particular condition being treated and the dosage required for therapeutic efficacy. The methods of this invention, generally speaking, may be practised using any mode of administration that is medically acceptable, meaning any mode that produces therapeutic levels of the active component of the invention without causing clinically unacceptable adverse effects. Such modes of administration include oral, rectal, topical, nasal, transdermal or parenteral (e.g. subcutaneous, intramuscular and intravenous) routes. In particular, the lipid extract of the present invention has been found to be active when administered orally, subcutaneously and transdermally.
Transdermal administration of the lipid extract is a particularly preferred administration mode, as the lipid extract has been found to have surprising anti-inflammatory activity when administered transdermally.
The compositions of this invention may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy. Such methods include the step of bringing the active component into association with a carrier which constitutes one or more accessory ingredients. In general, the compositions are prepared by uniformly and intimately bringing the active component into association with a liquid carrier, a finely divided solid carrier, or both, and then, if necessary, shaping the product.
Compositions of the present invention suitable for oral administration may be presented as discrete units such as capsules, cachets, tablets or lozenges, each containing a predetermined amount of the active component, in liposomes or as a suspension in an aqueous liquid or non-liquid such as a syrup, an elixir, or an emulsion.
Compositions suitable for parenteral administration conveniently comprise a sterile aqueous preparation of the active component which is preferably isotonic with the blood of the recipient. This aqueous preparation may be formulated according to known methods using those suitable dispersing or wetting agents and suspending agents. A sterile injectable preparation may be formulated as a sterile injectable solution or suspension in a nontoxic parenterally-acceptable diluent or solvent, for example as a solution in polyethylene glycol and lactic acid. Among the acceptable vehicles and solvents that may be employed are water, Ringer""s solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose, any bland fixed oil may be employed including synthetic mono-or di-glycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables.
Compositions suitable for transdermal administration conveniently comprise the active component in an ointment or lotion base or vehicle, and may include a skin penetration enhancing agent to assist in administration of the active component. Suitable bases or vehicles are oils such as olive or emu oil, administered alone or with a penetrant such as cineole or limonene.
Other delivery systems can include sustained release delivery systems. Preferred sustained release delivery systems are those which can provide for release of the active component of the invention in sustained release pellets or capsules. Many types of sustained release delivery systems are available. These include, but are not limited to: (a) erosional systems in which the active component is contain within a matrix, and (b) diffusional systems in which the active component permeates at a controlled rate through a polymer.
The formulation of such therapeutic compositions is well known to persons skilled in this field. Suitable pharmaceutically acceptable carriers and/or diluents include any and all conventional solvents, dispersion media, fillers, solid carriers, aqueous solutions, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like. The use of such media and agents for pharmaceutically active substances is well known in the art, and it is described, by way of example in Remington""s Pharmaceutical Sciences, 18th Edition, Mack Publishing Company, Pennsylvania, USA. Except insofar as any conventional media or agent is incompatible with the active component, use thereof in the pharmaceutical compositions of the present invention is contemplated. Supplementary active ingredients can also be incorporated into the compositions.
Oral or transdermal administration will be preferred for many conditions because of the convenience to the patient, although localised sustained delivery may be more desirable for certain treatment regimens.
The active component is administered in therapeutically effective amounts. A therapeutically effective amount means that amount necessary at least partly to attain the desired effect, or to delay the onset of, inhibit the progression of, or halt altogether, the onset or progression of the particular condition being treated. Such amounts will depend, of course, on the particular condition being treated, the severity of the conditions and individual patient parameters including age, physical condition, size, weight and concurrent treatment. These factors are well known to those of ordinary skill in the art and can be addressed with no more than routine experimentation. It is preferred generally that a maximum dose be used, that is, the highest safe dose according to sound medical judgement. It will be understood by those of ordinary skill in the art, however, that a lower dose or tolerable dose may be administered for medical reasons, psychological reasons or for virtually any other reasons.
It is especially advantageous to formulate compositions in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the human or animal patients to be treated; each unit containing a predetermined quantity of active component calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier and/or diluent. The specifications for the novel dosage unit forms of the invention are dictated by and directly dependent on (a) the unique characteristics of the active component and the particular therapeutic effect to be achieved, and (b) the limitations inherent in the art of compounding such an active component for the particular treatment.
Generally, daily doses of active component will be from about 0.01 mg/kg per day to 1000 mg/kg per day. Small doses (0.01-1 mg) may be administered initially, followed by increasing doses up to about 1000 mg/kg per day. In the event that the response in a subject is insufficient at such doses, even higher doses (or effective higher doses by a different, more localised delivery route) may be employed to the extent patient tolerance permits. Multiple doses per day are contemplated to achieve appropriate systemic levels of the active component.
Throughout this specification unless the context requires otherwise, the word xe2x80x9ccomprisexe2x80x9d, or variations such as xe2x80x9ccomprisesxe2x80x9d or xe2x80x9ccomprisingxe2x80x9d, will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers.